Nucleoside diphosphate kinase B contributes to arrhythmogenesis in human-induced pluripotent stem sell-derived cardiomyocytes from a patient with arrhythmogenic right ventricular cardiomyopathy
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, inheritable cardiac disorder characterized by ventricular tachyarrhythmias, progressive loss of cardiomyocytes with fibrofatty replacement and sudden cardiac death. The exact underlying mechanisms are unclear. Methods: Thi...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 February 2020
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| In: |
Journal of Clinical Medicine
Year: 2020, Jahrgang: 9, Heft: 2 |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm9020486 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/jcm9020486 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2077-0383/9/2/486 
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| Verfasserangaben: | Fanis Buljubasic, Ibrahim El-Battrawy, Huan Lan, Santosh K. Lomada, Anupriya Chatterjee, Zhihan Zhao, Xin Li, Rujia Zhong, Qiang Xu, Mengying Huang, Zhenxing Liao, Siegfried Lang, Lukas Cyganek, Xiaobo Zhou, Thomas Wieland, Martin Borggrefe and Ibrahim Akin |
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| 245 | 1 | 0 | |a Nucleoside diphosphate kinase B contributes to arrhythmogenesis in human-induced pluripotent stem sell-derived cardiomyocytes from a patient with arrhythmogenic right ventricular cardiomyopathy |c Fanis Buljubasic, Ibrahim El-Battrawy, Huan Lan, Santosh K. Lomada, Anupriya Chatterjee, Zhihan Zhao, Xin Li, Rujia Zhong, Qiang Xu, Mengying Huang, Zhenxing Liao, Siegfried Lang, Lukas Cyganek, Xiaobo Zhou, Thomas Wieland, Martin Borggrefe and Ibrahim Akin |
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| 520 | |a Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, inheritable cardiac disorder characterized by ventricular tachyarrhythmias, progressive loss of cardiomyocytes with fibrofatty replacement and sudden cardiac death. The exact underlying mechanisms are unclear. Methods: This study investigated the possible roles of nucleoside diphosphate kinase B (NDPK-B) and SK4 channels in the arrhythmogenesis of ARVC by using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Results: In hiPSC-CMs from a patient with ARVC, the expression levels of NDPK-B and SK4 channels were upregulated, the cell automaticity was increased and the occurrence rate of arrhythmic events was enhanced. Recombinant NDPK-B applied into hiPSC-CMs from either healthy donors or the patient enhanced SK4 channel current (ISK4), cell automaticity and the occurrence of arrhythmic events, whereas protein histidine phosphatase 1 (PHP-1), a counter actor of NDPK-B, prevented the NDPK-B effect. Application of PHP-1 alone or a SK4 channel blocker also reduced cell automaticity and arrhythmic events. Conclusion: This study demonstrated that the elevated NDPK-B expression, via activating SK4 channels, contributes to arrhythmogenesis in ARVC, and hence, NDPK-B may be a potential therapeutic target for treating arrhythmias in patients with ARVC. | ||
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